The effect of chronic morphine administration will be determined on acetylcholine (ACh) content, release, utilization and turnover in various regions of the rat brain. Eight major regions of the rat brain will be studied including the cerebral cortex, cerebellum, medulla oblongata, thalamus, hypothalamus, striatum, hippocampus and midbrain. Content and release of ACh will be measured by pyrolysis gas chromatography. Release will be obtained using the push-pull cannula technique. Utilization of brain ACh will be measured using the choline acetyltransferase inhibitor acetylseco hemicholinium. Turnover will be measured in rats given labeled choline during different phases of morphine dependence and withdrawal. Narcotic agonists like morphine, heroin, levorphan, meperidine and methadone will be compared with mixed agonists-antagonists like nalorphine and pure antagonists like naloxone. Both the daily chronic injections of morphine and morphine pellets implanted subcutaneously will be used. Natural, abrupt and naloxone- induced withdrawal will be compared. Some selected experiments will be done using the Macaca mulatta monkey as a species phylogenetically closer to man. This research will clarify the role of brain ACh in narcotic dependence and withdrawal and should lead to novel approaches to treating human narcotic dependence.